Dans cette étude nous avons utilisé le bisphénol A (BPA) comme polluant modèle pour analyser l'efficacité des différents processus de Fenton et photo-Fenton mis en place. Dans un premier temps nous avons étudié le processus de Fenton en présence du complexe Fe(III)-EDDS utilisé comme source de fer. Différents paramètres physico-chimiques (concentrations en H2O2, Fe(III)-EDDS, O2 et le pH) ont été testés afin d'optimiser l'efficacité du système en termes de dégradation du BPA. Parallèlement, le même type d'étude a été mené en présence de lumière (de 300 à 450 nm) afin d'étudier le processus de photo-Fenton. Dans les 2 cas nous avons mis en évidence un effet du pH peu commun puisque la dégradation de BPA est plus rapide et importante plus le pH est élevé dans une gamme allant de 3,0 à 9,0. Dans le but de comprendre le mécanisme mis en jeu des expériences d'inhibition de radicaux (*OH et HO2●/O2●-) ont été réalisées. Une des conclusions importantes de ce travail est que dans les deux systèmes le complexe Fe(III)-EDDS joue un rôle très positif pour la dégradation du BPA. De plus, nous avons également montré que ces processus étaient très efficaces pour des pH proches de la neutralité et faiblement basiques. La comparaison avec d'autres complexant du fer (EDTA, citrate, oxalate) montre qu'en présence du complexe Fe(III)-EDDS nous obtenons l'efficacité la plus importante. Ce résultat et le fait que les processus soient très efficaces à pH neutre ou faiblement basiques montrent que le complexe Fe(III)-EDDS est vraiment une source de fer très prometteuse dans les processus de Fenton et photo-Fenton. Dans une troisième partie nous avons regardé l'effet d'EDDS dans un système hétérogène en présence de Goethite comme source de fer. Dans ce chapitre il a été mis en évidence que l'EDDS inhibe le processus de Fenton, EDDS s'adsorbe fortement à la surface et limite la réactivité de H2O2 avec la surface de la Goethite. Par contre dans le processus de photo-Fenton, EDDS augmente l'efficacité de dégradation du BPA à pH proche de la neutralité et à faible concentration en H2O2.

abstract: Endocrine disruptors are chemicals that interact with the hormone system to negative effect. They ‘disrupt’ normal processes to cause diseases like vaginal cancer and obesity, reproductive issues like t-shaped uteri and infertility, and developmental abnormalities like spina bifida and cleft palate. These chemicals are ubiquitous in our daily lives, components in everything from toothpaste to microwave popcorn to plastic water bottles. My dissertation looks at the history, science, and regulation of these impactful substances in order to answer the question of how endocrine disruptors appeared, got interpreted by different groups, and what role science played in the process. My analysis reveals that endocrine disruptors followed a unique science policy trajectory in the US, rapidly going from their proposal in 1991 to their federal regulation in 1996, even amid intense and majority scientific disagreement over whether the substances existed at all. That trajectory resulted from the work of a small number of scientist-activists who constructed a concept and category as scientific, social, and regulatory. By playing actors from each sphere against each other and advancing a very specific scientific narrative that fit into a regulatory and social window of opportunity in the 1990s, those scientist-activists made endocrine disruptors a national issue that few could ignore. Those actions resulted in the Endocrine Disruptor Screening Program, a heavily-criticized and ineffective regulatory program. My dissertation tells a story of the past that informs the present. In 2018, the work of researchers, public media, and policymakers in the 1990s continues to play out, evident in the deep scientific division over endocrine disrupting effects and the inability of the European Union to settle on even a definition of endocrine disruptors for regulation purposes. / Dissertation/Thesis / Doctoral Dissertation Biology 2018

Bisfenol A (BPA) är ett propanderivat med två fenolgrupper. Det syntetiserades för första gången år 1905 av Thomas Zincke vid Marburgs universitet. När en polymerkemist upptäckte att det kunde användas för att bilda polykarbonatplaster växte dess popularitet. Idag är BPA-industrin en miljardindustri och många av oss använder dagligen plaster där denna kemikalie ingår. Nu har det gjorts nya toxikologiska undersökningar som visar att BPA kanske inte är så ofarligt som man tidigare trott. Vårt största intag av föreningen sker via mag-tarmkanalen genom att det kan läcka från olika slags plastföremål i kontakt med livsmedel. Enligt en panel sammansatt av USA:s National Institutes of Health finns det en risk för negativa effekter på hjärna och beteende hos barn. Reaktionerna på riskbedömningarna har varierat och detta examensarbete vill presentera några argument för vikten av att undersöka BPA: s hälsorisker mer. Syftet med detta examensarbete är att med en litteraturstudie undersöka en del av vad som finns dokumenterat om BPA: s hälsorisker för människan, typ av genomförda toxikologiska undersökningar och hur dessa resultat har påverkat företag och länder. Denna litteraturstudie visar att det finns stor bredd på tolkningen av de toxikologiska studiernas resultat och därmed är det osäkert om det finns hälsorisker eller inte. Det finns omdebatterade resultat som tyder på en ökad risk av toxikologiska effekter, till exempel skada på hjärta hos barn men det finns ingen fastställd hälsorisk för människor. Mer standardisering behövs i forskningen för att ge den en högre kvalitet och göra studier mer jämförbara. / Bisphenol-A (BPA) is a propane derivative with two phenol groups. It was synthetisized for the first time in the year of 1905 by Thomas Zincke at the Marburg University. When a polymer chemist discovered that it could be used to form polycarbonate plastics its popularity grew. Today the chemistry of BPA is a billion industry and many of us use daily plastics in which this chemical is used for. Many new toxicological studies have shown that BPA maybe is not as friendly as before thought. Our biggest exposure to it is orally because it can leak from different plastics with contact to food. According to a panel assembled by USA’s National Institutes of Health there is a risk of negative effects on brain and behaviour on children. The reactions of the risk assessment have been different and this thesis wants to show some arguments for the importance of exploring the health risks of BPA more. The purpose of this thesis is to use a literature study to investigate a part of what is documented about the health effects of BPA on humans, the kind of toxicological studies performed and how their results have affected companies and countries. The literature study shows that the width of interpretation of the toxicological studies’ results is big and thus that it is uncertain if there are health effects or not. There are some uncertain results facts funded on conflict that show a heightened risk for toxicological effects, for example damage on heart and changes in behavior in infants but there is no empirically stated health risk in humans. More standardization in research is needed for giving it a higher quality and thus making it more comparable.

Master of Science / Department of Chemical Engineering / Larry E. Erickson / Polycarbonate products have been used extensively world wide for decades because they are lightweight, shatter-resistant and considered to be safe. Polycarbonate is a thermoplastic that is used to make compact discs, phones, lenses, and food contact products such as water bottles, baby bottles and food storage containers. For more than half century, there has been interest in polycarbonate (PC) products and the monomer bisphenol-A (BPA) because BPA can leach from food polycarbonate containers. The environmental fate for both chemicals in air, water and soil is of interest, also. To understand the fate of polycarbonate, its main degradation pathways, main degradation mechanisms and main products are reviewed. These pathways are thermal degradation, photo-degradation and hydrolysis under different conditions. Furthermore, key topics like PC degradation kinetics and PC chemical resistance are part of this comprehensive discussion. The biodegradation of BPA has been thoroughly studied. About twelve lab methods for environmental fate are summarized and reviewed to understand the “big picture” for BPA degradation. This includes screening tests, which assess the ready and inherent degradability, to simulation tests for surface waters, soils and wastewater treatment systems. The testing of all methods is examined under conditions close to the real environment fate. Furthermore, the fate distribution for BPA based on the Equilibrium Criterion Model (EQC) model is reviewed. Extensive research on polycarbonate and BPA has been conducted in the last fifty years. During this time, both chemicals have been studied and tested by industry and government agencies. The pharmacological test results from major studies indicate that consumer exposure to BPA at concentrations normally experienced in daily living does not pose a risk to human health. On the other hand, minor toxicological studies indicate potential risks to human health. Research on health and safety are continuing.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20227号 / 医博第4186号 / 新制||医||1019(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 増永 慎一郎, 教授 宮本 享, 教授 伊佐 正 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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Small proteins are difficult to study at high resolution with single-particle cryo-electron microscopy (cryo-EM). In general, sample properties such as large size (> 80 kDa), symmetry and rigidity are key to utilize this technology. To facilitate structural studies of small proteins as well, using cryo-EM, this project aims to incorporate a photo-inducible cross-link in a large and symmetric scaffold that is amenable for study, and covalently bind small proteins of interest to this scaffold. The scaffold in this project consists of rabbit muscle aldolase (157 kDa in tetrameric state) with an engineered affibody affinity protein (7 kDa) attached to the N-terminus of each aldolase monomer via a rigid helix fusion. The affibody-domain of the scaffold will be cross-linked to small proteins of structural interest, with a focus on a model target consisting of a second affibody with affinity for the affibody displayed on the aldolase scaffold. Photoconjugation of the affibody Zwt was performed to crosslink both the Fc of IgG and the anti-idiotypic affibody Z963, revealing that a methionine acceptor in the target is preferable but not necessary for UV crosslinking using BPA. Binding of affibodies rigidly displayed on of the scaffold to targets such as affibodies and antibody fragments was demonstrated , using surface plasmon resonance (SPR). / Att studera små protein vid hög upplösning med enpartikelsrekonstruktion i kryo-elektronmikroskopi (kryo-EM) är utmanande. Generellt så krävs stora (> 80 kDa), symmetriska och stabila protein för att använda sig av kryo-EM. Med målet att möjliggöra strukturbestämning och strukturella studier av små protein, så ska detta projekt föra in en foto-aktiverad korslänk i ett stort och symmetriskt bärarprotein. Bäraren består av aldolas från kaninmuskel (157 kDa som tetramer) med en affibody (7 kDa) kopplad till N-terminalen av varje aldolas-monomer via en rigidt fuserad helix. Affibody-domänen av bärarproteinet kan bilda korslänkar till små protein vars struktur sedan kan studeras. Fokus i projektet är ett modellprotein som består av en annan affibody som binder den affibody i bäraren. Fotokonjugering av affibodyn Zwt utfördes för att skapa korslänkar till både Fc av IgG, samt den anti-idiotypiska affibodyn Z963, vilket påvisade att en metionin-mottagare i målproteinet är fördelaktigt för UV korslänkning med BPA, men inte ett krav. Affinitet av affibodies i bärarproteinet till målprotein såsom andra affibodies och antikroppsfragment påvisades.

The causes of errors in the angle of impact calculation were investigated including the surface type, falling velocity and the method used to fit an ellipse to a bloodstain. As had been cited previously the angle of impact was generally underestimated, especially at acute angles and the reason for this was determined to be due to an overestimation of the length of a bloodstain. The surface type was found to significantly affect the accuracy of an angle of impact calculation and as the falling velocity increased, the angle of impact calculation became more accurate. High-speed photography was used to further investigate the formation of bloodstains on surfaces. It was found that the formation of the bloodstain varied depending on the surface type and the angle of the surface. Bloodstain pattern analysis involves the application of scientific techniques to reconstruct events that resulted in a bloodstain pattern. The position of the blood source in three-dimensional space is a fundamental element of this application. Currently little is known about the methods used by bloodstain pattern analysts to select bloodstains when determining the region of origin. Fourteen analysts worldwide were surveyed in order to ascertain this information. It was found that the methods used were variable and were often not based on scientific research. Research was therefore undertaken into bloodstain selection and in particular, which bloodstains should be selected for a region of origin analysis. As a result of these experiments, two sets of selection criteria were established, one for use when the region of origin is being calculated manually and one for when directional analysis is being used.